Free PSA is the component of PSA not bound to proteins ("free") measured in ng/mL.Free PSA % is the ratio of Free PSA to PSA that is used with elevated or high PSA test levels to increase screening effectiveness. See our Free PSA page that opens in a new window.

A corresponding high PHI provides additional early warning because high PHI is associated with higher probabilities of prostate cancer found by biopsy.

Your "Underlying" "True" PSA and PHI are the values that your physicians should use to assess your risk with the help of prostate cancer risk calculators or rules of thumb about threshold level of concern. Learn about risk calculators in the Blog post: Use prostate cancer risk calculators to avoid premature biopsy that opens in a new window.

Your "True" PSA is Hybritech calibrated and adjusted for specific medications to treat prostate enlargement (BPH). See the Blog post:Elevated PSA? Is your "True" PSA higher? that opens in a new window.

Your "True" PHI is already Hybritech calibrated for use with the ERSPC Risk Calculator and popular look-up tables.

Your "Underlying" "True" PSA test level may be lower than your most recent "True" elevated PSA value because of temporary infection, inflammation or aggravation of your prostate. See the Blog post: Elevated PSA? Is your "Underlying" PSA lower? that opens in a new window.

Your "Underlying" "True" PHI may be lower than your most recent "True" PHI for the same reasons, especially Infections of the prostate and urinary tract that tend to decrease the Free PSA % component of PHI when they increase PSA.Follow-up testing is highly recommended for a long enough period for a possible infection to clear. See the Blog post: "Underlying" Free PSA, Prostate Health Index (PHI), 4Kscore, PCA3 in a new window.

Free PSA is the component of PSA not bound to proteins ("free") that responds differently than PSA:

Prostate cancer tends to decrease the ratio of Free PSA to PSA (Free PSA %) when it increases PSA.

Many non-cancer prostate conditions tend not to decrease Free PSA % when they increase PSA, such as prostate enlargement. Free PSA % tends to "weed out" these conditions and increase screening effectiveness.

Infections of the prostate and urinary tract tend to decrease Free PSA % when they increase PSA, which limits the effectiveness of Free PSA %.

Pro2PSA is a subset of Free PSA associated with prostate cancer. The ratio of Pro2PSA to Free PSA is higher for prostate cancer than it is for non-cancer conditions, which increases screening effectiveness.

PHI is superior to PSA because the PHI formula incorporates the ratio of Pro2PSA to Free PSA with the square root of PSA.

3. Interpret Your PHI, Elevated or High PSA and Prostate Volume

For any PSA level, the probability of cancer increases as PHI increases.

What Is the Probability of Significant Cancer for PHI and PSA Levels?

Only the overall probability of cancer is reported for four ranges of PHI shown on the Beckman Coulter website based on a 2015 study of PHI in the Journal of Urology (PubMed abstract will open in a new window). The probability of high-grade cancer is not reported, although it is related to the overall probability.

The highly regarded ERSPC Risk Calculator estimates the probability of significant prostate cancer (high-grade and large low-grade) and the probability of any prostate cancer. There you will learn of the many factors that affect the probability of prostate cancer. We use the ERSPC-RC to estimate probabilities of significant prostate cancer.

Notice that the probability of significant cancer increases steeply as Free PHI increases. The three curves show that the probability increases modestly as PSA increases because PSA is also considered by PHI.

Click to enlarge.

What Is the Probability of Significant Cancer for PHI and Prostate Volume?

Using the ERSPC-RC, we focus next on PHI and prostate volume for men with no other risk factors. For PSA 3.0, the graph on the right plots the probability significant prostate cancer will be found by biopsy as a function of PHI for three prostate volumes estimated by digital rectal exam (DRE): small (25cc), medium (40cc) and large (60cc).

Notice that the probabilities are much higher for a small prostate (the top red curve) than for a large prostate (the bottom blue curve). The probability of cancer is lower for large prostates because they tend to produce more PSA that "explains" elevated levels of PSA.

At an elevated PSA of 3.0 and PHI of 20, the estimated probability of significant prostate cancer is:

18% for a small 25cc DRE prostate volume

11% for a medium 40cc DRE prostate volume

7% for a large 60cc DRE prostate volume

Click to enlarge.

The dramatic difference in risk for small and large prostates demonstrates why it is so important to consider prostate volume for elevated PSA levels. The risk level of 10% is the same at 8 PHI for a small prostate as at 31 PHI for a large prostate. Full interpretation of PHI depends on prostate volume.

Ask your physician to estimate your prostate volume by digital rectal exam (DRE). Ask for a transrectal ultrasound (TRUS) to measure your prostate volume more accurately before considering a biopsy. To learn more see our Ultrasound-Based Prostate Cancer Smart Screening Analysis page in a new window.

Free PSA and PSA are two of the three key components of PHI. Although the effects of infection on PHI have not been studied, there is analysis of the effects of infection on PSA and Free PSA %.

For example, some men experience periodic infections of the prostate or urinary tract that cause their PSA to increase temporarily and their Free PSA % to decrease temporarily It would be a big mistake to use a temporarily increased PSA and decreased Free PSA % to assess underlying prostate cancer risk or estimate growth rate in PSA from cancer.

PSA Pattern for Periodic Infections

Click to enlarge.

The graph shows 10 annual PSA tests that vary up and down with a slow underlying increase. The PSA peaks reflect temporary infection and/or inflammation. The lower PSA tests may reflect underlying conditions, such as prostate enlargement (BPH) or cancer.

Enhanced blood tests used with prostate cancer risk calculators can substantially improve prostate cancer screening effectiveness compared to PSA alone. We describe and compare six combinations of enhanced blood and urine tests and risk calculators. See our Compare PSA, Free PSA, PHI, 4Kscore, PCA3 page in a new window for our full comparison.

The Prostate Health Index (PHI) is one of several enhanced test alternatives for prostate cancer screening.Free PSA and 4Kscore blood tests and PCA3 urine test are alternative enhanced tests that you can learn about in new windows.

Six Enhanced Test Combinations for Elevated and High PSA Test Levels (T1 to T6)

We consider six enhanced test combinations of blood and urine tests and risk calculators:

T1. Free PSA and PSA Blood Tests and Free PSA % Look-Up Table

T2. Free PSA and PSA Blood Tests and PCPT Risk Calculator

T3. Prostate Health Index (PHI) Blood Tests, Calculation and Report

T4. PHI Blood Tests, Calculation and ERSPC Risk Calculator

T5. 4Kscore Blood Tests, Calculation and Report

T6. PCA3 Urine Test and Report

The two PHI enhanced test combinations (T3 and T4) are described below:

Unfortunately, the probability of high-grade cancer is not reported, although it is related to the overall probability; and overall cancer probability is reported only in four ranges rather than as a continuous variable.You must operate the ERSPC Risk Calculator to estimate the probability of high-grade cancer as a continuous variable.

Consideration of prostate volume greatly increases the effectiveness of the ERSPC Risk Calculator. A 2012 World Journal of Urology very large European and US multi-institutional study shows the importance of prostate volume in the ERSPC-RC for screening effectiveness (PubMed abstract in a new window).

​​However, someone must operate the ERSPC Risk Calculator, and most physicians do not have the time to operate it and explain the process and results to you.​

Therefore, your willingness to operate the ERSPC Risk Calculator or to find someone to operate it is the threshold question for this option.

Many people learn and operate the ERSPC Risk Calculator in 15 to 25 minutes. Take a look at the ERSPC Risk Calculators in a new window, open the Risk Calculator 3 and 4 with TRUS or DRE and the Result of the Phi Test and give it a try before deciding to use or reject it.

Comparison of Enhanced Test Combinations for Elevated and High PSA Test Levels

Cost and Reimbursement

PHI: about $100 according to a 2016 Wall Street Journal Article but could be more. Often reimbursed - FDA approved.

PCA3: $200 to $450 range according to a Healthline.com article. Not FDA approved for screening. Medicare and many insurance companies do not pay for PCA3 for screening, according to a Healthline.com article.

periodic or annual enhanced tests in the future (unless prostate cancer is diagnosed)

Your screening costs can build up if the price is high and you are not reimbursed or if the price is high and your deductibles and co-pays are high.Moreover, your health insurance carrier may resist follow-up and periodic or annual enhanced tests, especially if the price is high.

Summary Comparison and Suggestions for Elevated or High PSA

There are three best enhanced test options with ranking based on what is important to you. Consideration of ​prostate volume (or not) is the biggest difference between PHI with ERSPC Risk Calculator using prostate volume and other alternatives.

If you are willing to operate the ERSPC Risk Calculator (and especially if either cost or consideration of prostate volume and TRUS ultrasound results are important to you) then consider:​

If you are concerned about operating the ERSPC Risk Calculator, we encourage you to enlist the help of a daughter, son, spouse or friend or even pay a student with computer skills.

Alternatively, we can operate the ERSPC Risk Calculator for you and create a full smart prostate cancer screening strategy report for you. Learn more about Prostate Smart Screening for Cancer at our home page in a new window.

6. ​Develop Your Prostate Smart Screening Strategy for Your PHI Level

For men who want to lead a collaborative team effort rather than be a passive patient.

Highlights of Prostate Smart Cancer Screening Strategy Analysis

Some very brief highlights may interest you in learning more about Prostate Smart Screening Strategy Analysis:

1. Understand Your "Underlying" "True" Elevated or High PSA

Your "Underlying" "True" elevated or high PSA is the value that your physicians should use to assess your risk with the help of prostate cancer risk calculators or rules of thumb. Adjust for WHO calibration and BPH treatment. For an elevated or high PSA, consider possible temporary infection, inflammation and prostate aggravation rather than prostate cancer as the cause.

2. ​Take Informative Screening Actions Using New Technology after Elevated or High PSA

For example using the ERSPC Risk Calculator, we focus on the Prostate Health Index (PHI) and prostate volume for men with no other risk factors. For an elevated PSA 3.0, the graph on the right plots the probability significant prostate cancer will be found by biopsy as a function of PHI for three prostate volumes estimated by digital rectal exam (DRE): small (25cc), medium (40cc) and large (60cc).

Notice that the probabilities are much higher for a small prostate (the top red curve) than for a large prostate (the bottom blue curve). The probability of cancer is lower for large prostates because they tend to produce more PSA that "explains" elevated levels of PSA.

Many men find it helpful to translate risk calculator results into potential loss of life expectancy that is easier to understand and use for decision making. Worrisome probabilities from risk calculators often imply very little loss of life expectancy.

Project past trends to help identify a surprise increase in PSA that may be caused by temporary prostatitis

Estimate growth rate of PSA from cancer that may suggest the growth rate in cancer to use for analysis of biopsy delay

For example, very fast growing prostate cancers that produce fast growing PSA are relatively rare but very dangerous. PSA can grow to very high levels in a few years unless identified early. See graph at right.

In contrast, slow growing cancers that produce slow growing PSA may pose little or no threat with biopsy delay the best strategy.

Most elevated or high PSA is not caused by cancer. Prostatitis caused by infection and/or inflammation and prostate enlargement caused by benign prostatic hyperplasia (BPH) are more frequent causes of elevated or high PSA than prostate cancer. Moreover, these non-cancer conditions can cause PSA to vary up and down around an increasing PSA trend.

Click to enlarge.

6. Estimate Your Growth Rate of Cancer Risk to Inform Delay Decision

Most prostate cancers seem to be slow growing. A PSA trend provides the best estimate of prostate cancer growth because increasing PSA is associated with increasing risk of prostate cancer found by biopsy and increasing risk of death if found.

7. ​Consider Your Potential Loss of Life Expectancy from Delay of Premature Biopsy

Premature biopsy is the major risk of PSA testing!

Biopsy for prostate cancer is the pivotal screening step with a choice between now and delay.

Delay defers the risks of sepsis, emotional costs of possible diagnosis and potential over-treatment with risk of impotence and incontinence.

Delay reduces life expectancy if cancer is present. However, many men are surprised by the typically very small overall risk of delay.

Many men would choose biopsy delay because they are not very concerned about a small loss of life expectancy, often at the end of life when they they expect their quality of life to be low. They prefer delay to avoid a premature biopsy with sepsis risk, possible diagnosis, treatment and side effects, including impotence and incontinence.